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Abstract

In cellular respiration, cytochrome c transfers electrons from the cytochrome bc₁ complex to cytochrome c oxidase by transiently binding to the membrane proteins. The first X-ray structure of the yeast cytochrome bc₁ complex with bound cytochrome c revealed the general architecture of the electron-transfer complex. The interface of the complex is small. The haem moieties are centrally located in a mainly non-polar contact site, which includes a cation-pi interaction and is surrounded by complementary charged residues. Only one cytochrome c₁-docking site of the dimeric complex is occupied with cytochrome c. The recent 1.9 Å (1 Å=0.1 nm) resolution structure of the complex showed that the interface is highly hydrated. With cytochrome c bound, a higher number of interfacial water molecules are present on the cytochrome c₁ interface, whereas its protein surface is not affected. Remarkably, the dimer structure is slightly asymmetric. Univalent cytochrome c binding coincides with conformational changes of the Rieske head domain and subunit QCR6p. Pronounced hydration and a mobility mismatch at the interface with disordered charged residues on the cytochrome c side are favourable for transient binding. Comparison with a new structure of the complex with bound isoform-2 cytochrome c led to the definition of a core interface, which refers to four common interaction pairs including the cation-pi interaction. They encircle the haem groups and are surrounded by variable interactions. The core interface may be a feature to gain specificity for formation of the reactive complex. The consistency in the binding interaction despite differences in primary sequence, redox state and crystal contacts, together with crystallization at physiological ionic strength, clearly suggest that the structures show the native bound state of the electron-transfer complex.